Fiber scaffolds for use in esophageal prostheses

ABSTRACT

The development and construction of implantable artificial organs, and a process for manufacturing three-dimensional polymer microscale and nanoscale structures for use as scaffolds in the growth of biological structures such as hollow organs, luminal structures, or other structures within the body are disclosed.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application claims priority to U.S. Provisional Application No.61/466,039, filed Mar. 22, 2011, entitled “Electrospinning for HighlyAligned Nanofibers,” U.S. Provisional Patent Application No. 61/562,090,filed Nov. 21, 2011, entitled “Nanofiber Scaffolds for BiologicalStructures,” and U.S. Provisional Patent Application No. 61/585,869,filed Jan. 12, 2012, entitled “Biocompatible Nanofiber Materials forBiological Structures,” the entire contents of which are hereinincorporated by reference.

BACKGROUND OF THE INVENTION

The esophagus is an organ within the neck that permits travel of foodand saliva from the mouth to the stomach through peristalsis. It has agenerally tubular shape consisting of multiple layers ranging from amucosa layer on the lumen consisting primarily of epithelial cells to amuscular adventitia consisting primarily of smooth muscle cells,striated muscle cells and fibroblasts. The inner layer of muscle isoriented in a circumferential direction while the outer layer of muscleis oriented in a longitudinal direction (see FIG. 1). When at rest, theesophagus is nearly collapsed, but can expand to roughly 3 cm indiameter upon swallowing.

Peristalsis involves involuntary movements of the longitudinal andcircular muscles, primarily in the digestive tract but occasionally inother hollow tubes of the body, that occur in progressive wavelikecontractions. Peristaltic waves occur in the esophagus, stomach, andintestines. The waves can be short, local reflexes or long, continuouscontractions that travel the whole length of the organ, depending upontheir location and what initiates their action. In the esophagus,peristaltic waves begin at the upper portion of the tube and travel thewhole length, pushing food ahead of the wave into the stomach. Particlesof food left behind in the esophagus initiate secondary peristalticwaves that remove leftover substances. One wave travels the full lengthof the tube in about nine seconds. Peristaltic waves start as weakcontractions at the beginning of the stomach and progressively becomestronger as they near the distal stomach regions. The waves help to mixthe stomach contents and propel food to the small intestine. Usually,two to three waves are present at one time in different regions of thestomach, and about three waves occur each minute.

In the large intestine (or colon), the peristaltic wave, or massmovement, is continuous and progressive; it advances steadily toward theanal end of the tract, pushing waste material in front of the wave. Whenthese movements are vigorous enough to pass fecal masses into therectum, they are followed by the desire to defecate. If feces are passedto the rectum and not evacuated from the body, they are returned to thelast segment of the colon for longer storage by reverse peristalticwaves. Peristaltic waves are particularly important in helping to removegas from the large intestine and in controlling bacterial growth bymechanically acting as a cleansing agent that dislodges and removespotential colonies of bacteria.

Partial loss or complete loss of peristalsis due to the loss of theesophagus, small intestine and/or large intestine due to cancer or otherdiseases can have a catastrophic, if not fatal, effect on an animal. Anumber of in vivo prostheses for luminal structures such as theesophagus are known. Typically these prostheses are formed by donorstructures from cadavers or are manmade structures. However, theseexisting structures are subject to failure due to anastomotic stenosis,luminal stenosis, infection, dislocation, and migration, among othercauses. Therefore, there is an ongoing need for artificial or prostheticversions of organs such as the esophagus and intestinal tract that willprovide the patient, human or otherwise, with a functioning replacementfor the lost organ.

DESCRIPTION OF THE DRAWINGS

The file of this patent contains at least one photograph or drawingexecuted in color. Copies of this patent with color drawing(s) orphotograph(s) will be provided to the Patent and Trademark Office uponrequest and payment of necessary fee

The accompanying drawings, which are incorporated into and form a partof the specification, schematically illustrate one or more exemplaryembodiments of the invention and, together with the general descriptiongiven above and detailed description given below, serve to explain theprinciples of the invention, and wherein:

FIG. 1a is an illustration of the anatomy of the esophagus from Frank H.Netter and FIG. 1b is an illustration of a portion of the smallintestine;

FIG. 2 is a photograph of an exemplary fiber deposition system, inaccordance with the present invention;

FIGS. 3A, 3B, 3C and 3D provide several photographs of examples ofrelatively small and large diameter tubes and irregular shapes derivedfrom electrospun fiber made with the process of the present invention;

FIGS. 4A, 4B, 4C and 4D provide a number of photographs illustrating thecontrol of cell orientation and differentiation based on discrete fiberalignment;

FIGS. 5A and 5B provide photographs of a 200 nm diameter fiber (on theleft) with pore sizes of a few microns and a 20 um diameter fiber (onthe right) with pore sizes of around 50 um; and

FIG. 6 is an SEM image of composite fiber scaffold that includes bothoriented fibers and random fibers.

DESCRIPTION OF THE INVENTION

Exemplary embodiments of the present invention are now described withreference to the Figures. Although the following detailed descriptioncontains many specifics for purposes of illustration, a person ofordinary skill in the art will appreciate that many variations andalterations to the following details are within the scope of theinvention. Accordingly, the following embodiments of the invention areset forth without any loss of generality to, and without imposinglimitations upon, the claimed invention.

The present invention relates generally to the development andconstruction of implantable artificial organs, and more specifically toa process for manufacturing three-dimensional polymer microscale andnanoscale structures for use as scaffolds in the growth of biologicalstructures such as hollow organs, luminal structures, or otherstructures within the body, particularly the esophagus (see FIG. 1A)and/or the small intestine (see FIG. 1B), large intestine, duodenum, andjejunum. Exemplary versions of the manufacturing process of thisinvention include preparing a preform that is based on an actual organ;electro spinning one or more layers of nanoscale (less than 1000nanometers) or microscale (less than 50 microns) polymer fibers on thepreform to form a nanofiber based scaffold. The fibers are typicallyformed by electrospinning by extruding a polymer solution from afiberization tip; creating an electronic field proximate to thefiberization tip; and positioning a ground or opposite polarity withinthe preform. The preform may be rotated to align the fibers on thepreform or a second ground or polarity may be placed in the preform andrapidly switching the electric field to align the fibers. The microscaleand nanoscale polymer fibers may be randomly aligned or maybesubstantially parallel or both (see FIG. 6). These nanofiber structuresmay be seeded with one or more types of biological cells prior toimplantation in the body to increase the rate of tissue growth into thescaffold. The scaffold may include autologous or allogenic cells such ascord blood cells, embryonic stem cells, induced pluripotent cells,mesenchymal cells, placental cells, bone marrow derived cells,hematopoietic cell, epithelial cells, endothelial cells, fibroblasts,chondrocytes or combinations thereof.

Choosing a material that accurately mimics the mechanical properties ofthe native esophagus (or other organ) can promote proper stem celldifferentiation and facilitate normal esophageal function such asperistalsis. Materials may be non-resorbable for permanent implantationor may be designed to slowly degrade while the host body rebuilds thenative tissue until the implanted prosthesis is completely resorbed.Permanent polymers may include polyurethane, polycarbonate, polyesterterephthalate and degradable materials may include polycaprolactone,polylactic acid, polyglycolic acid, gelatin, collagen, or fibronectin.The fibers may be electrospun onto a preform with the desired prosthesisshape (see FIG. 2). FIG. 2 is a photograph of an exemplary setup of a 5mm diameter rod with electrospun fiber being deposited onto the surface.The exemplary mandrel is coated with Teflon to facilitate removal of thescaffold after deposition or a slight taper (≈1°) can be manufacturedinto the mandrel. Nearly any size or shape can be produced from theelectrospun fibers by using a pre-shaped form and deposition method asshown in FIGS. 3A-3D.

Closely mimicking the structural aspects of the native esophagus (orother organ) is important with regard to replicating the function of thenative esophagus. By controlling the orientation of the fibers andassembling a composite structure of different materials and/or differentfiber orientations it is possible to control and direct cell orientationand differentiation (see FIGS. 4A-4D). Fiber orientation can be alteredin each layer of a composite or sandwich scaffold in addition to thematerial and porosity to most closely mimic the native tissue. Aproperly constructed scaffold will permit substantially completecellular penetration and uniform seeding for proper function andprevention of necrotic areas developing. If the fiber packing is toodense, then cells may not be able to penetrate or migrate from theexposed surfaces into the inner portions of the scaffold. However, ifthe fiber packing is not close enough, then the attached cells may notbe able to properly fill the voids, communicate and signal each otherand a complete tissue or organ may not be developed. Controlling fiberdiameter can be used to change scaffold porosity as the porosity scaleswith fiber diameter (see FIGS. 5A-5B). Alternatively, blends ofdifferent polymers may be electrospun together and one polymerpreferentially dissolved to increase scaffold porosity. The propertiesof the fibers can be controlled to optimize the fiber diameter, thefiber spacing or porosity, the morphology of each fiber such as theporosity of the fibers or the aspect ratio, varying the shape from roundto ribbon-like. The precursor solution described below may be controlledto optimize the modulus or other mechanical properties of each fiber,the fiber composition, the degradation rate (from rapidly biosoluable tobiopersitent. The fibers may also be formed as drug eluting fibers,anti-bacterial fibers or the fibers may be conductive fibers, radioopaque fibers to aid in positioning or locating the fibers in an x-ray,CT or other scan.

The effects of mechanical strain on electrospun polymer scaffolds hasbeen described in the literature (see, Microstructure-PropertyRelationships in a Tissue Engineering Scaffold, Johnson et al., Journalof Applied Polymer Science, Vol. 104, 2919-2927 (2007) and QuantitativeAnalysis of Complex Glioma Cell Migration on ElectrospunPolycaprolcatone Using Time-Lapse Microscopy, Johnson et al., TissueEngineering; Part C, Volume 15, Number 4, 531-540 (2009), which areincorporated by reference herein, in their entirety, for all purposes).Strains as low as 10% appear to rearrange and align the fibers in thedirection of loading. This alignment increases with the applied strainuntil over 60% of the fibers are aligned within ±10% of the direction ofapplied stress. If cells are present during fiber rearrangement in vivoor in vitro, they could conceivably be affected by these changesdepending on the overall rate of strain. Fiber alignment is retainedfollowing a single cycle of extension and release. This has significantbiological implications for a broad array of future tissue-engineeringoperations. As cells move across such a substrate, biased motion islikely as locomotion is based on forming and then dissolving a series offocal adhesions. Formation of these adhesions along the fiber directionmay be easier than those perpendicular to that direction although thiswill be partially controlled by the spacing between the fibers. This haslonger-term consequences for the eventual control of the architecture oftissues that develop upon such substrates.

Cellular mobility parallel to the fiber direction means that one couldconceivably control and direct cell proliferation and migration byprestraining scaffolds to align the fibers in certain directions. Thiscould result in tailored structures with highly aligned fibers and, as aresult, highly aligned cells. Of additional importance is the fact thatmany envisioned applications of tissue-engineering scaffolds willinvolve the use of cyclic stresses designed to achieve specificarchitectures in the biological component of the developing tissue. Ifthe scaffold experiences continuing hysteresis in which orientationincreases versus the number of cycles the efficiency of the overallprocess will be greatly enhanced. For blood vessels, as an example, theapplication of cyclic pressures will produce preferential stresses thatcould cause significant alignment of the fibers in the circumferentialdirection. This could cause cellular alignment in the circumferentialdirection, potentially creating a more biomimetic arrangement.

Within the context of this invention, electrospinning is driven by theapplication of a high voltage, typically between 0 and 30 kV, to adroplet of a polymer solution or melt at a flow rate between 0 and 50ml/h to create a condition of charge separation between two electrodesand within the polymer solution to produce a polymer jet. A typicalpolymer solution would consist of a polymer such as polycaprolactone,polystyrene, or polyethersulfone and a solvent such as1,1,1,3,3,3-Hexafluoro-2-propanol, N,N-Dimethylformamide, Acetone, orTetrahydrofuran in a concentration range of 1-50 wt %. As the jet ofpolymer solution travels toward the electrode it is elongated into smalldiameter fibers typically in the range of 0.1-30 μm.

In preparing an exemplary scaffold, a polymer nanofiber precursorsolution is prepared by dissolving 2-30 wt % polyethylene terephthalate(PET) (Indorama Ventures) in a mixture of1,1,1,3,3,3-hexafluoroisopropanol and trifluoroacetic acid and thesolution is heated to 60° C. followed by continuous stirring to dissolvethe PET. The solution may be cooled to room temperature and the solutionplaced in a syringe with a blunt tip needle. The nanofibers are formedby electrospinning using a high voltage DC power supply set to 1 kV-40kV positive or negative polarity, a 5-30 cm tip-to-substrate distance,and a 1 μl/hr to 100 mL/hr flow rate. It is possible to use a needlearray of up to 1,000's of needles to increase output. Approximately0.2-3 mm thickness of randomly oriented and/or highly-aligned fibers maybe deposited onto the form, and polymer rings added, followed by anadditional approximately 0.2-3.0 mm of fiber added while the form isrotated. The scaffold may placed in a vacuum overnight to ensure removalof residual solvent (typically less than 10 ppm) and treated using aradio frequency gas plasma for 1 minute to make the fibers morehydrophilic and promote cell attachment.

In accordance with this invention, an exemplary preparation ofelectrospinning solution typically includes of polyethyleneterephthalate (PET), polycaprolactone (PCL), polylactic acid (PLA),polyglycolic acid (PGA), polyetherketoneketone (PEKK), polyurethane(PU), polycarbonate (PC), polyamide (Nylon), natural polymers such asfibronectin, collagen, gelatin, hyaluronic acid or combinations thereofthat are mixed with a solvent and dissolved. A form is prepared for thedeposition of nanofibers. Optionally, simulated cartilage or othersupportive tissue may be applied to the form and the fibers are thensprayed onto or transferred onto a form to build up the scaffold. Thepresent invention may be useful for the preparation of a number ofbodily tissues, including hollow organs, three-dimensional structureswithin the body such as trachea, esophagus, intestine or luminalstructures, such as nerves (epineurium or perineurium), veins andarteries (aorta, tunica externa, external elastic lamina, tunica medica,internal elastic lamina, tunica inima). Other preforms for mammals suchas primates, cats, dogs, horses and cattle may be produced.

While the present invention has been illustrated by the description ofexemplary embodiments thereof, and while the embodiments have beendescribed in certain detail, it is not the intention of the Applicant torestrict or in any way limit the scope of the appended claims to suchdetail. Additional advantages and modifications will readily appear tothose skilled in the art. Therefore, the invention in its broaderaspects is not limited to any of the specific details, representativedevices and methods, and/or illustrative examples shown and described.Accordingly, departures may be made from such details without departingfrom the spirit or scope of the applicant's general inventive concept.

For example, the present invention encompasses the following exemplaryembodiments and variants thereof: (i) a composite scaffold seeded withstem cells and promoted to differentiate into stratified tissue; (ii)separate scaffold layers or sheets seeded independently to formdifferent types of tissue and then assembled together using sutures,adhesive or welding to form a tubular shape and the stratified tissue;(iii) a scaffold implanted without cells for immediate replacement ofdamaged tissue and allow for cellular migration in vivo; (iv) anelectrospun fiber scaffold made from non-resorbable materials such aspolyethylene terephthalate, polyurethane, polycarbonate, poly etherketone ketone; (v) an electrospun fiber scaffold made from resorbablematerials such as polycaprolactone, polylactic acid, polyglycolic acid;(vi) an electrospun fiber scaffold made from natural polymers such ascollagen, gelatin, fibronectin, hyaluronic acid or any combination ofmaterial types; (vii) an electrospun fiber scaffold made from a singlelayer of oriented fibers or a composite comprising layers of orientedfiber to correspond to the native structure and help orient anddifferentiate cells (fiber orientation can be from a rotating mandrel(circumferential fiber alignment), a translating mandrel (longitudinalfiber alignment), or split ground method of using electrostatics toalign the fiber); (viii) using a pre-shaped mandrel or form to depositfibers onto to achieve a near net shaped esophagus or intestine or otherorgans that support/perform peristalsis—the pre-shaped form can have aslight taper machined into the mandrel or coated with a non-sticksurface to allow easy removal of the scaffold; and (ix) using apre-shaped mandrel or form to deposit fibers onto to achieve a near netshaped esophagus segment/patch or intestine segment/patch or other organsegment/patch that supports/performs peristalsis. A pre-shaped form canhave a slight taper machined into the mandrel or coated with a non-sticksurface to allow easy removal of the scaffold.

What is claimed:
 1. An implantable artificial organ comprising: ascaffold comprising at least one layer of electrospun fibers having anorientation, a diameter, and a fiber spacing configured to control theorientation, growth, or differentiation of biological cells seededthereon, the scaffold formed into a replica of a biological organselected from the group consisting of an esophagus, a small intestine, alarge intestine, a duodenum, and a jejunum; wherein the scaffold has aninterior surface that is smooth on the microscale; wherein theelectrospun fibers comprise a radiopaque material; and wherein theelectrospun fibers have a fiber spacing of about 2 micrometers to about50 micrometers.
 2. The implantable artificial organ of claim 1, whereinthe electrospun fibers are selected from the group consisting of anon-resorbable material, a resorbable material and a combinationthereof.
 3. The implantable artificial organ of claim 1, wherein theelectrospun fibers comprise one or more of the following: apolyurethane, a polycarbonate, a polyester, a polycaprolactone, apolylactic acid, a polyglycolic acid, a polyetherketoneketone, apolyamide, a gelatin, a collagen, a hyaluronic acid, and a fibronectin.4. The implantable artificial organ of claim 1, wherein the electrospunfibers have a diameter from about 100 nanometers to about 1000nanometers.
 5. The implantable artificial organ of claim 1, wherein theelectrospun fibers have a diameter from about 100 nanometers to about 50micrometers.
 6. The implantable artificial organ of claim 1, wherein theelectrospun fibers have a shape selected from round and ribbon-like. 7.The implantable artificial organ of claim 1, wherein the electrospunfibers have an orientation selected from the group consisting ofsubstantially mutually parallel, randomly oriented, and a combinationthereof.
 8. The implantable artificial organ of claim 1, wherein theelectrospun fibers comprise substantially a single material.
 9. Theimplantable artificial organ of claim 1, wherein the electrospun fiberscomprise a mixture of multiple materials.
 10. The implantable artificialorgan of claim 1, wherein the electrospun fibers further comprise one ormore of an elutable drug and an anti-bacterial material.
 11. Theimplantable artificial organ of claim 1, wherein the at least one layerof electrospun fibers comprises a plurality of layers of electrospunfibers.
 12. The implantable artificial organ of claim 11, wherein theelectrospun fibers of each layer of the plurality of layers ofelectrospun fibers comprise a first material.
 13. The implantableartificial organ of claim 11, wherein the electrospun fibers of at leastone layer of the plurality of layers of electrospun fibers comprise afirst material, and the electrospun fibers of at least a second layer ofthe plurality of layers of electrospun fibers comprise a secondmaterial.
 14. The implantable artificial organ of claim 11, wherein theelectrospun fibers of each layer of the plurality of layers ofelectrospun fibers have a first diameter.
 15. The implantable artificialorgan of claim 11, wherein the electrospun fibers of at least one layerof the plurality of layers of electrospun fibers have a first diameter,and the electrospun fibers of at least a second layer of the pluralityof layers of electrospun fibers have a second diameter.
 16. Theimplantable artificial organ of claim 11, wherein the electrospun fibersof each layer of the plurality of layers of electrospun fibers have afirst orientation.
 17. The implantable artificial organ of claim 11,wherein the electrospun fibers of at least one layer of the plurality oflayers of electrospun fibers have a first orientation, and theelectrospun fibers of at least a second layer of the plurality of layersof electrospun fibers have a second orientation.
 18. The implantableartificial organ of claim 11, wherein the electrospun fibers of eachlayer of the plurality of layers of electrospun fibers have a firstfiber spacing.
 19. The implantable artificial organ of claim 11, whereinthe electrospun fibers of at least one layer of the plurality of layersof electrospun fibers have a first fiber spacing, and the electrospunfibers of at least a second layer of the plurality of layers ofelectrospun fibers have a second fiber spacing.
 20. The implantableartificial organ of claim 1, wherein the at least one layer ofelectrospun fibers comprises a plurality of electrospun fibers.
 21. Theimplantable artificial organ of claim 20, wherein at least one of theplurality of electrospun fibers comprises a first material, and at leasta second of the plurality of electrospun fibers comprises a secondmaterial.
 22. The implantable artificial organ of claim 20, wherein atleast one of the plurality of electrospun fibers has a first diameter,and at least a second of the plurality of electrospun fibers has asecond diameter.
 23. An implantable artificial organ comprising: ascaffold comprising: at least one layer of electrospun fibers having anorientation, a diameter, and a fiber spacing configured to control theorientation, growth, or differentiation of biological cells seededthereon, the scaffold formed into a replica of a biological organselected from the group consisting of an esophagus, a small intestine, alarge intestine, a duodenum, and a jejunum; and a plurality ofbiological cells seeded on the scaffold; wherein the scaffold has aninterior surface that is smooth on the microscale; wherein theelectrospun fibers comprise a radiopaque material; and wherein theelectrospun fibers have a fiber spacing of about 2 micrometers to about50 micrometers.
 24. The implantable artificial organ of claim 23,wherein the plurality of biological cells comprises one or more ofautologous cells and allogeneic cells.
 25. The implantable artificialorgan of claim 23, wherein the plurality of biological cells comprisesone or more of the following: cord blood cells, embryonic stem cells,induced pluripotent cells, mesenchymal cells, placental cells, bonemarrow derived cells, hematopoietic cells, epithelial cells, endothelialcells, fibroblast cells, and chondrocyte cells.
 26. The implantableartificial organ of claim 23, wherein the at least one layer ofelectrospun fibers comprises a plurality of layers of electrospunfibers.
 27. The implantable artificial organ of claim 11, wherein atleast a first layer of the plurality of layers of electrospun fibers isseeded with a plurality of a first type of biological cells, and atleast a second layer of the plurality of layers of electrospun fibers isseeded with a plurality of a second type of biological cells.
 28. Amethod for fabricating an implantable artificial organ scaffold, themethod comprising: depositing, by electrospinning, at least a firstlayer of polymer fibers onto a preform, wherein the deposited polymerfibers have an orientation, a diameter, and a fiber spacing configuredto control the orientation, growth, or differentiation of biologicalcells seeded thereon; forming the scaffold into a replica of abiological organ selected from the group consisting of an esophagus, asmall intestine, a large intestine, a duodenum, and a jejunum whereinthe scaffold has an interior surface that is smooth on the microscale,wherein the electrospun fibers comprise a radiopaque material; andwherein the electrospun fibers have a fiber spacing of about 2micrometers to about 50 micrometers; and removing the at least firstlayer of polymer fibers from the preform.
 29. The method of claim 28,wherein a shape of the preform is based at least in part on a structureof a biological organ.
 30. The method of claim 28, wherein a shape ofthe preform is based at least in part on a computer model.
 31. Themethod of claim 28, wherein electro spinning comprises: extruding apolymer solution from a fiberization tip; creating an electronic fieldproximate to the fiberization tip; and providing a ground or oppositepolarity in the preform.
 32. The method of claim 31, wherein the preformis rotated about an axis.
 33. The method of claim 31, wherein thepreform is translated longitudinally.
 34. The method of claim 28,further comprising subjecting the at least first layer of polymer fibersto at least one mechanical stress.
 35. The method of claim 28, furthercomprising subjecting the at least first layer of polymer fibers to aplurality of cycles of an applied mechanical stress.
 36. The method ofclaim 28, further comprising seeding the at least first layer of polymerfibers with a plurality of biological cells.
 37. The method of claim 28,wherein depositing, by electrospinning, at least a first layer ofpolymer fibers onto a preform, comprises depositing, by electrospinning,a plurality of layers of polymer fibers onto the preform.
 38. The methodof claim 37 further comprising: seeding a plurality of a first type ofbiological cell onto at least a first layer of polymer fibers; andseeding a plurality of a second type of biological cell onto at least asecond layer of polymer fibers.
 39. A method of implanting an artificialorgan in a patient in need thereof comprising implanting in the patientthe implantable artificial organ of claim
 1. 40. The method of claim 39,further comprising seeding the artificial organ with a plurality ofbiological cells.
 41. An implantable artificial organ comprising: ascaffold comprising a first layer of electrospun fibers having a firstorientation, and a second layer of electrospun fibers deposited over thefirst layer, the second layer having a second orientation different fromthe first orientation, the scaffold formed into a replica of abiological organ having a luminal structure, wherein the scaffold has aninterior surface that is smooth on the microscale; wherein theelectrospun fibers comprise a radiopaque material; and wherein theelectrospun fibers have a fiber spacing of about 2 micrometers to about50 micrometers.
 42. The implantable artificial organ of claim 41,wherein the biological organ is selected from the group consisting of anesophagus, a small intestine, a large intestine, a duodenum, a jejunum,and a blood vessel.
 43. The implantable artificial organ of claim 1,further comprising at least one acellular, non-electrospun supportivematerial having a shape of at least a portion of a ring, wherein the atleast one layer of electrospun fibers is deposited on at least a portionof the at least one acellular, non-electrospun supportive material.